DESCRIPTION: Chlamydia pneumoniae is a common human respiratory pathogen. Recent studies have associated this organism with atherosclerotic disease of the coronary and carotid arteries by seroepidemiological studies and detection of the organism within lesions. Because coronary heart disease is a leading cause of death in the United States, the goal of the proposed work is to determine if C. pneumoniae infection plays ar role in atherosclerosis. The proposal is based on the development of a novel experimental mouse model of chronic C. pneumoniae infection of atheromas. The mouse models that will be used are ApoE-deficient transgenic and C57BL/6 mice. ApoE-deficient mice develop atherosclerosis spontaneously on a regular diet and atherosclerosis in C57BL mice can be induced by feeding with a highfat/high cholesterol diet. Both of these strains of mice are susceptible to intranasal inoculation with C. pneumoniae, and the infection disseminates to the aorta and persists in atheroma. The specific aims are: 1) to use ApoE mice fed a regular diet to study if C. pneumoniae infection alters the progression and severity of atherosclerotic lesions determined by histopathology and computer assisted morphometry; 2) to use C57BL mice fed either a normal or atherogenic diet to study if C. pneumoniae induces any vascular pathology and/or if C. pneumoniae is a co-factor to lipids for atherogenesis; and 3) to evaluate if antimicrobial chemotherapy effective against chlamydiae, i.e. - doxycycline and azithromycin, prevents or reverses the course of C. pneumoniae in atherogenesis. If C. pneumoniae is determined to play a role in atherogenesis, vaccine prevention and treatment of C. pneumoniae infection may be considered in the future to reduce the risk of atherosclerosis.